Antifactor Xa Levels versus Activated Partial Thromboplastin Time for Monitoring Unfractionated Heparin

Abstract

Intravenous unfractionated heparin (UFH) remains an important therapeutic agent, particularly in the inpatient setting, for anticoagulation. Historically, the activated partial thromboplastin time (aPTT) has been the primary laboratory test used to monitor and adjust UFH. The aPTT test has evolved since the 1950s, and the historical goal range of 1.5-2.5 times the control aPTT, which first gained favor in the 1970s, has fallen out of favor due to a high degree of variability in aPTT readings from one laboratory to another, and even from one reagent to another. As a result, it is now recommended that the aPTT goal range be based on a corresponding heparin concentration of 0.2-0.4 unit/ml by protamine titration or 0.3-0.7 unit/ml by antifactor Xa assay. Given that several biologic factors can influence the aPTT independent of the effects of UFH, many institutions have transitioned to monitoring heparin with antifactor Xa levels, rather than the aPTT. Clinical data from the last 10-20 years have begun to show that a conversion from aPTT to antifactor Xa monitoring may offer a smoother dose-response curve, such that levels remain more stable, requiring fewer blood samples and dosage adjustments. Given the minimal increased acquisition cost of the antifactor Xa reagents, it can be argued that the antifactor Xa is a cost-effective method for monitoring UFH. In this review, we discuss the relative advantages and disadvantages of the aPTT, antifactor Xa, and protamine titration tests, and provide a clinical framework to guide practitioners who are seeking to optimize UFH monitoring within their own institutions.

Pyrazolyl-Tetrazoles and Imidazolyl-Pyrazoles as Potential Anticoagulants and their Integrated Multiplex Analysis Virtual Screening

“…57,58 Our experimental results show how the newly in silico designed pyrazoleimidazoline compounds present a similar behavior to direct FXa inhibitors, with dose-response curves detectable by routine coagulation tests of PT and APTT.…”

Correlación de valores de TTPa con anti factor Xa para establecer rango terapéutico en tratamiento anticoagulante con heparina sódica

“…En consideración de estas ventajas podría plantearse su uso rutinario en la monitorización de HNF, pero esto no ha sido posible debido a limitaciones en disponibilidad de acceso, complejidad técnica y alto costo. A pesar de esto, algunos centros las han incorporado en sus esquemas de monitorización [9][10][11]18 . Considerando la evidencia disponible, la recomendación vigente de sociedades como el American College of Chest Physicians 3 y otras 6,19 , es corregir los valores de RT por TTPa con métodos de determinación más exactos en cada laboratorio y cada vez que se modifique la técnica de la prueba de TTPa.…”

“…Considerando lo anterior, para mejorar la calidad y seguridad del tratamiento con HNF, la recomendación vigente es correlacionar los valores de TTPa con otro examen que tenga una mayor sensibilidad y especificidad previo a su uso en la monitorización de la dosificación de heparina. Aunque no existen estudios prospectivos con distribución aleatoria, la determinación de niveles de heparina medidos en plasma bajo técnica de titulación de protamina y la medición de valores de anti factor Xa han sido utilizadas como exá-menes de referencia para el TTPa en múltiples publicaciones [3][4][5][6][7][8][9][10][11][12][13] , correspondiendo el RT para éstas de 0,2 a 0,4 UI/ml para la primera y de 0,3 a 0,7 UI/ml para la segunda. Es importante señalar que este tipo de rectificación debe ser realizada en cada laboratorio y debe repetirse cada vez que se cambien los reactivos o el coagulómetro.…”

Practical Value of Anti-Xa Activity in the Evaluation of Extracorporeal Circuit Anticoagulation during Haemodialysis: Results of a Cross-Sectional Single-Centre Study

“…The APTT is used for monitoring therapy with UFH but is thought to be less appropriate for guiding LMWH dosage due to its relative insensitivity to LMWHs [15] . However, as the APTT depends on the factor Xa available in patient plasma, we hypothesized that significant LMWH levels during dialysis would also reflect in the APTT.…”

“…An important factor that introduces variability in the anti-Xa activity measured is the addition versus omission of exogenous antithrombin to the anti-Xa assay, which has been previously shown in the estimation of UFH and rivaroxaban concentrations [13,14] . Some anti-Xa reagents contain antithrombin to correct for in vivo antithrombin deficiency, as LMWHs need to complex with antithrombin to be able to bind and deactivate factor Xa [15] . Especially in patients with long-term use of LMWH, acquired antithrombin deficiency can develop when antithrombin production does not equal antithrombin loss through clearance of the LMWH-antithrombin complex, as was also found for patients on long-term UFH therapy [16] .…”